Context: Newborns with ambiguous genitalia or males with nonpalpable gonads usually require an early assessment of the presence and functional state of testicular tissue. Objective: Our objective was to characterize the precise ontogeny of the serum patterns of gonadotropins, testosterone, anti-Müllerian hormone (AMH), and inhibins in normal newborn boys. Design: We conducted a cross-sectional and longitudinal study. Subjects: Serum samples were obtained in 57 boys and 13 girls on d 2 of life. A second sample was obtained on d 7, 10, 15, 20, and 30 (boys) and on d 30 (girls). Main Outcome Measures: Serum levels of gonadotropins, testosterone, AMH, and inhibins were measured. Results: In males, LH and FSH were undetectable or very low on d 2. By d 7, LH increased to 3.94 ± 3.19 IU/liter (mean ± sd) and FSH to 2.04 ± 1.67 IU/liter. LH/FSH ratios were 0.40 ± 0.11 (d 2) and 2.02 ± 0.20 (d 30). AMH rose from 371 ± 168 pmol/liter (d 2) to 699 ± 245 pmol/liter (d 30), and inhibin B rose from 214 ± 86 ng/liter (d 2) to 361 ± 93 ng/liter (d 30). The inhibin α-subunit precursor (pro-αC) remained stable during the first month of life. Testosterone levels were 66 ± 42 ng/dl (d 2), 82 ± 24 ng/dl (d 20), and 210 ± 130 ng/dl (d 30). A sexual dimorphism was observed in AMH and inhibin B (lower in girls on d 2 and 30), in LH/FSH ratio (lower in girls on d 30) and in testosterone (lower in girls on d 30). Conclusions: Sertoli cell markers AMH and inhibin B are the earliest useful markers indicating the existence of normal testicular tissue.

Obesity, metabolic syndrome, and type 2 diabetes, three strongly interrelated diseases, are associated to increased morbidity and mortality worldwide. The pathogenesis of obesity-associated disorders is still under study. Secreted protein acidic and rich in cysteine (SPARC) is a matricellular glycoprotein expressed in many cell types including adipocytes, parenchymal, and non-parenchymal hepatic cells and pancreatic cells. Studies have demonstrated that SPARC inhibits adipogenesis and promotes insulin resistance; in addition, circulating SPARC levels were positively correlated with body mass index in obese individuals. Therefore, SPARC is being proposed as a key factor in the pathogenesis of obesity-associated disorders. The aim of this study is to elucidate the role of SPARC in glucose homeostasis. We show here that SPARC null (SPARC^−/−) mice displayed an abnormal insulin-regulated glucose metabolism. SPARC^−/− mice presented an increased adipose tissue deposition and an impaired glucose homeostasis as animals aged. In addition, the absence of SPARC worsens high-fat diet-induced diabetes in mice. Interestingly, although SPARC^−/− mice on high-fat diet were sensitive to insulin they showed an impaired insulin secretion capacity. Of note, the expression of glucose transporter 2 in islets of SPARC^−/− mice was dramatically reduced. The present study provides the first evidence that deleted SPARC expression causes diabetes in mice. Thus, SPARC deficient mice constitute a valuable model for studies concerning obesity and its related metabolic complications, including diabetes.

BACKGROUND: Premature ovarian failure (POF) is characterized by hypergonadotropic amenorrhoea before the age of 40. Inhibin α-subunit (INHα) gene is proposed as a candidate gene due to its role in negative feedback control of FSH. METHODS: Polymorphism –16C>T of INHα gene was studied in 61 POF patients and 82 controls above 40 years old (C > 40). Substitution 769G>A was studied in 59 POF patients, 76 C > 40 and 73 controls below 40 years old (C < 40). RESULTS: No significant difference in risk of POF development for –16T allele was found when comparing idiopathic POF (I-POF) with C > 40 (Odds ratio = 1.46; 95% confidence interval = 0.63–3.19). Implication of –16C>T polymorphism in serum inhibin levels was analysed in 46 controls, and no significant differences (P > 0.05) were found between CC and CT + TT genotype groups when comparing either mid-follicular phase Pro-αC and inhibin B values or mid-luteal phase Pro-αC and inhibin A values. Heterozygosity for substitution 769G>A was found in 1 of 59 POF woman, 2 of 76 C > 40 and 6 of 73 C < 40. Presence of this substitution in a relevant number of control subjects is herein described for the first time. CONCLUSION: Our results indicate that –16C>T and 769G>A variants in INHα gene may not be associated to POF disease.

We aimed to describe the functional changes of Sertoli cells, based on the measurement of serum anti-Müllerian hormone (AMH) and inhibin B during treatment with GnRHa and after its withdrawal in boys with central precocious puberty. Six boys aged 0.8 to 5.5 yr were included. AMH was low at diagnosis in patients >1 yr but within the normal range in younger patients. AMH increased to normal prepubertal levels during treatment. After GnRHa withdrawal, AMH declined concomitantly with the rise in serum testosterone. At diagnosis, inhibin B was elevated and decreased throughout therapy, remaining in the upper normal prepubertal range. In patients with testicular volume above 4 mL AMH remained higher in spite of suppressed FSH. After treatment withdrawal, inhibin B rose towards normal pubertal levels. In conclusion, AMH did not decrease in patients <1 yr reflecting the lack of androgen receptor expression in Sertoli cells in early infancy. Serum inhibin B might result from the contribution of two sources: the mass of Sertoli cells and the stimulation exerted by FSH. Sertoli cell markers might provide additional tools for the diagnosis and treatment followup of boys with central precocious puberty.